NEW YORK (Reuters Health) - A transcription factor linked to type 2 diabetes seems to regulate the expression of a large number of genes, not just one or two, new research indicates. The effects of the factor, HNF4alpha, are contrary to what was expected.
Diabetes has been shown to occur when only one copy of the HNF4alpha gene is present, lead author Dr. Duncan T. Odom told Reuters Health. “This makes HNF4alpha an obvious therapeutic target,” he said. “If you can find a drug that upregulates the activity of HNF4alpha then you’re going to have a serious treatment for diabetes.”
Given the association with type 2 diabetes, Dr. Odom’s team decided to look at the extent to which HNF4alpha and related factors control gene expression in the pancreas and liver.
The current report is published in the February 27th issue of Science.
“Previous studies have largely used indirect methodologies to determine how transcriptional regulation occurs in the pancreas and liver,” Dr. Odom, from the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, noted. In contrast, “our methods were direct-we pinpointed the promoters where the transcription factors were binding,” he said.
“With our approach, we thought that we would find one or two key genes that were involved in diabetes,” Dr. Odom said. “We were quite surprised to find that HNF4alpha bound to about 13% of genes on the genome. It is a startlingly wide-acting transcription factor.”
The findings “gain significance in the light of recent reports describing a link between the HNF4alpha gene and late-onset type 2 diabetes,” write Drs. Rohit Kulkarni and C. Ronald Kahn, from Harvard Medical School, Boston, Massachusetts, in a related editorial.
“Defining the regulatory networks that link upstream signals, like insulin, to the regulation of HNFs and their target genes could provide insights into the pathophysiology of this epidemic disease,” they conclude.
Source: Science 2004;303:1378-1381. [ Google search on this article ]
MeSH Headings:Biological Sciences: Biology: Gene Expression Regulation: Genetics: Genetics, Biochemical: Molecular Biology: Transcription Factors: Biological SciencesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
